Missing Gene Makes Mice Lean

JEFF MILLER
Mice lacking a single gene can feast on a high-fat diet without gaining weight, researchers report. The findings, published online this week by the Proceedings of the National Academy of Sciences, throw new light on the genetic mechanisms underlying metabolism.

The gene, known as SCD1, encodes an enzyme (SCD) involved in synthesizing monounsaturated fatty acids. Previous research has implicated high SCD activity in a variety of disorders, including obesity, diabetes and atherosclerosis. In the new work, James M. Ntambi of the University of Wisconsin and his colleagues found that mice missing SCD1 managed to avoid gaining weight and developing diabetes despite eating a diet laden with fat. Rather than accumulating in the liver or other tissues as it normally would, the fat was metabolized. "We have biochemical evidence that the mice burn the excess fat," Ntambi notes. "The protection from obesity involves increased energy expenditure and increased oxygen consumption."

There are drawbacks to lacking SCD1, however: a number of the altered mice developed skin and eye problems as they aged. But other studies conducted by Ntambi and his collaborators indicate that mice that produce half the level of the SCD enzyme are normal. Drugs aimed at suppressing the fatty acids produced by SCD, Ntambi says, may therefore offer protection against obesity and diabetes without the side effects.